2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one | 1366267-98-2

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one
• 英文别名: 2-[5-(4-Methoxyphenyl)-3-phenyl-3,4-dihydropyrazol-2-yl]-1,3-thiazol-4-one
• CAS: 1366267-98-2
• 化学式: C₁₉H₁₇N₃O₂S
• 分子量: 351.429
• InChiKey: MHPKGGGCCZJCKM-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.3
• 重原子数：
  25
• 可旋转键数：
  4
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.21
• 拓扑面积：
  79.6
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one 、 4-甲酰苯氧基乙酸 在 sodium acetate 、 溶剂黄146 作用下， 以95 %的产率得到(Z)-2-(4-((2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)-4-oxothiazol-5(4H)-ylidene)methyl)phenoxy)acetic acid
  参考文献：
  名称：

  用于抗炎剂噻唑/噻唑烷棒状吡唑啉衍生物设计的片段合并方法：合成、生物药理学评价和分子建模研究

  摘要：

  应用片段合并方法设计噻唑/噻唑烷酮棒状吡唑啉衍生物5a-e、6a-c、7和10a-d作为 COX-2 和 5-LOX 双重抑制剂。化合物5a、6a和6b是最有效的 COX-2 选择性抑制剂（IC 50 = 0.03–0.06 μM，SI = 282.7–472.9），对 5-LOX 具有高活性（IC 50  = 4.36–4.86 μM），而化合物5b和10a是活性和选择性5-LOX抑制剂，IC 50 分别为2.43和1.58 μM。大多数活性候选物6a的体内测定和组织病理学检查显示，与标准药物相比，炎症显着减少，安全性更高。化合物6a表现出与参考 COX-2 和 5-LOX 抑制剂（分别为塞来昔布和槲皮素）相同的方向和结合相互作用。因此，化合物6a已被确定为进一步优化和开发安全有效的抗炎药物的潜在先导化合物。

  DOI：

  10.1016/j.bioorg.2023.106724
• 作为产物：
  描述：

  苯甲醛 在 sodium acetate 、 乙酸酐 、 溶剂黄146 、 potassium hydroxide 作用下， 以 乙醇 、 水 为溶剂， 反应 12.0h， 生成 2-(3-(4-methoxyphenyl)-5-phenyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one
  参考文献：
  名称：

  Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors

  摘要：

  A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC50 = 0.24 mu M for EGFR and IC50 = 1.07 mu M for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC50 value of 0.30, 0.54, and 0.70 mu M, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.bmc.2012.01.051

文献信息

• Design, synthesis and biological evaluation of pyrazolyl-thiazolinone derivatives as potential EGFR and HER-2 kinase inhibitors
  作者：Ke-Ming Qiu、Hai-Hong Wang、Li-Ming Wang、Yin Luo、Xian-Hui Yang、Xiao-Ming Wang、Hai-Liang Zhu

  DOI：10.1016/j.bmc.2012.01.051

  日期：2012.3

  A series of pyrazolyl-thiazolinone derivatives (E1-E36) have been designed and synthesized and their biological activities were also evaluated as potential EGFR and HER-2 kinase inhibitors. Thirty-four of the 36 compounds were reported for the first time. Among them, compound 2-(5-(4-bromophenyl)-3-p-tolyl-4,5-dihydro-1H-pyrazol-1-yl)thiazol-4(5H)-one (E28) displayed the most potent inhibitory activity (IC50 = 0.24 mu M for EGFR and IC50 = 1.07 mu M for HER-2). Antiproliferative assay results indicated that compound E28 owned high antiproliferative activity against MCF-7, B16-F10 and HCT-116 in vitro, with IC50 value of 0.30, 0.54, and 0.70 mu M, respectively. Docking simulation was further performed to position compound E28 into the EGFR active site to determine the probable binding model. Based on the preliminary results, compound E28 with potent inhibitory activity in tumor growth would be a potential anticancer agent. (C) 2012 Elsevier Ltd. All rights reserved.
• Fragment merging approach for the design of thiazole/thiazolidine clubbed pyrazoline derivatives as anti-inflammatory agents: Synthesis, biopharmacological evaluation and molecular modeling studies
  作者：Mohamed K. Elgohary、Soha R. Abd El Hadi、Mahmoud F. Abo-Ashour、Mohammed E. Abo-El Fetoh、Hassan Afify、Hatem A. Abdel-Aziz、Sahar M. Abou-Seri

  DOI：10.1016/j.bioorg.2023.106724

  日期：2023.10

  Fragment merging approach was applied for the design of thiazole/thiazolidinone clubbed pyrazoline derivatives 5a-e, 6a-c, 7 and 10a-d as dual COX-2 and 5-LOX inhibitors. Compounds 5a, 6a, and 6b were the most potent and COX-2 selective inhibitors (IC50= 0.03–0.06 μM, SI = 282.7–472.9) with high activity against 5-LOX (IC50 = 4.36–4.86 μM), while compounds 5b and 10a were active and selective 5-LOX

  应用片段合并方法设计噻唑/噻唑烷酮棒状吡唑啉衍生物5a-e、6a-c、7和10a-d作为 COX-2 和 5-LOX 双重抑制剂。化合物5a、6a和6b是最有效的 COX-2 选择性抑制剂（IC 50 = 0.03–0.06 μM，SI = 282.7–472.9），对 5-LOX 具有高活性（IC 50  = 4.36–4.86 μM），而化合物5b和10a是活性和选择性5-LOX抑制剂，IC 50 分别为2.43和1.58 μM。大多数活性候选物6a的体内测定和组织病理学检查显示，与标准药物相比，炎症显着减少，安全性更高。化合物6a表现出与参考 COX-2 和 5-LOX 抑制剂（分别为塞来昔布和槲皮素）相同的方向和结合相互作用。因此，化合物6a已被确定为进一步优化和开发安全有效的抗炎药物的潜在先导化合物。